title: Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier.
abstract: Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(γ-benzyl L-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability, size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was encapsulated in the micelles. The drug release profile, in vivo distribution and the cytotoxicity against hepatic carcinoma QGY-7703 cells of DOX-loaded micelles were studied. The results indicated that the release profile was pH-dependent with Fickian diffusion kinetics. The micelles were remarkably targeted to the liver, inducing a 4.9-fold higher DOX concentration than that for free DOX · HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX · HCl, and the cytotoxicity was time- and dosage-dependent. These results suggest that GA-functionalized micelles represent a promising carrier for drug delivery to the liver.
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Chuang-Nian
authors.initials: CN
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Tian
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Wang
authors.forename: Rui-Tao
authors.initials: RT
authors.lastname: Cha
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001673:Biodegradation, Environmental; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006034:Glycyrrhetinic Acid / Q000737:chemistry*; D022781:Hepatocytes / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D008823:Micelles; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D008823:Micelles; D011108:Polymers; C003172:poly-gamma-benzyl-L-glutamate; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D006034:Glycyrrhetinic Acid